Despite tremendous advances in medicine, patients who are under drug therapy or radiotherapy usually suffer from cytotoxicity or side effects attributed to the systemic administration of drugs, or the side effects of radiotherapy such as the mutation or death of normal cells. The accurate delivery of drugs such as contrast agents or therapeutic agents to target tissues could allow for the diagnosis or therapy of diseases without causing side effects in normal cells or tissues. Accordingly, extensive research has been directed toward drug targeting in order to diagnose or treat diseases without side effects.
Drug targeting or targeted drug delivery is typically accomplished by chemically or physically linking a drug with an antibody, a peptide, a ligand, or a polymer specific for or targeting tissues or cells to which the drug is to be delivered. However, physiochemical properties of drugs do not always permit easy linkage with antibodies, peptides, ligands, etc. Further, if used for chemical or physical bonding, a binder or a stabilizer may cause negative effects on pharmaceutical properties or biotoxicity of drugs. Hence, there is still a technical need for drug targeting methods free of such problems.
Of targeted drug delivery methods for killing cancer cells, photothermal therapy using gold nanoparticles may be applied for the effective treatment of cancer. Gold nanoparticles, ranging in size up to tens of nanometers, exhibit intrinsic optical properties through the quantumization of surface electrons, and find applications in a variety of fields including single electron devices, chemical sensors, biosensors, drug delivery, and catalysts. For instance, Professor Halas and Professor West's research team at Rice University synthesized a gold nanoshell and applied it to thermal therapy for the necrosis of cancer cells. The gold nanoparticle is a nanostructure composed of a silica core coated with a gold nanoshell. Depending on the ratio of thickness between the core and the outer shell, the light absorption wavelength can be adjusted from a visible light range to a near infrared (NIR) range. The research team synthesized a gold nanoshell having a large NIR absorption cross section. The gold nanoshell was conjugated at the surface with an antibody specific for cancer cells, and then was applied to cancer cells and irradiated with an NIR continuous wave laser. The NIR light absorbed by the gold nanoshell was converted into heat by which cancer cells can be effectively necrotized. Less apt to be absorbed into biological tissues, light in an NIR region of 800 nm to 1200 nm can reach deeper in the biological tissues than can visible light. Hence, irradiation of NIR light can bring about a desirable thermal treatment effect, with the production of a minimal incision area.
However, conventional synthesis methods of gold nanoparticles, such as chemical reductive reactions, typically need the use of metal compounds, solvents, reducing agents, or stabilizers. One of main barriers to the use of gold nanoparticles in the medical field is the toxicity caused by such chemical additives.
In addition, the production of stable gold nanoparticles requires a surface modification. When they are subjected to a pH change or are highly concentrated, gold nanoparticles, if not surface modified, undergo condensation due to structural instability, and are altered in size and morphology. Therefore, an additional surface stabilization technology must be needed for gold nanoparticles. For use in drug targeting, gold nanoparticles allow antibodies or targeting peptides to be exposed on the surface thereof via a chemical linkage. In this regard, uniform exposure of antibodies or peptides at a high density is a limitative point.
Generally, sodium citrate is used as a condensation nucleus for metal ions in synthesizing gold nanoparticles. At a pH of 7.0 or higher, tyrosine can offer a standard reduction potential at which gold ions can be reduced. Thus, a peptide containing such amino acids can be used to reduce gold ions and produce gold nanoparticles stabilized on the surface of the peptide (KR2012-0052501). However, the method disclosed in KR2012-0052501 is merely a technique in which gold-affinitive proteins or gold ion reducing peptides are reacted with gold precursors to aggregate gold nanoparticles around the proteins or peptides. Thus, this method is not only difficult to apply to the morphological or dimensional control of gold nanoparticles, but also requires additional chemical linkages for providing target directionality.